The immune system uses antigen receptors on T cells (TCRs) to detect antigens, such as peptides or glycolipids that are presented by antigen-presenting molecules present on the surface of antigen-presenting cells. The antigen presenting molecules, termed Major Histocompatibility proteins have evolved to present peptides, while the structurally related CD1 family has evolved to bind glycolipids that are bound in deep and hydrophobic binding grooves. Upon binding of the TCR to the MHC or CD1 bound antigen, the T cell becomes activated, leading to the production of cytokines, second messenger molecule, that activate other immune cells for a full immune response to counter an infection, in the case of foreign antigens. We have found that peptides can also be presented by CD1d, and that certain peptides can activate T cells that are considered specific for certain glycolipid antigens. Our lab uses Xray crystallography to investigate at the atomic level the binding of the antigen-receptor to the peptide antigen when presented by CD1d in order to understand the structural requirements for T cell activation. This knowledge will lead to the design of altered peptide ligands that can be selected to either enhance the immune response to infection or to change the cytokine profile, increased production of either pro- inflammatory or anti-inflammatory cytokines, to help ameliorate autoimmune diseases, such as diabetes or multiple sclerosis.